Dataset Information

Dupilumab Significantly Modulates Pain and Discomfort in Patients With Atopic Dermatitis: A Post Hoc Analysis of 5 Randomized Clinical Trials.

ABSTRACT:

Background

Pain is a frequent symptom of atopic dermatitis (AD).

Objectives

The aims of the study were to evaluate the effects of dupilumab on pain/discomfort in AD and to determine whether pain correlates with other outcomes.

Methods

This was a post hoc analysis of 5 randomized, placebo-controlled clinical trials in which adults with chronic AD received placebo or dupilumab 300 mg every 2 weeks or once weekly with and without topical corticosteroids. Proportions of patients with no pain/discomfort on this dimension of the 5-dimension EuroQoL (EQ-5D) at week 16 (all trials) and week 52 (CHRONOS) were compared between placebo and dupilumab. Correlations were evaluated between pain/discomfort and signs and symptoms of AD.

Results

Among 2632 evaluated patients, 72.9% to 83.1% reported at least moderate pain/discomfort at baseline. Higher proportions treated with dupilumab reported no pain/discomfort at week 16 relative to placebo; risk differences ranged from 22.3% (95% confidence interval = 11.5%-33.1%) to 42.2% (95% confidence interval = 26.6%-57.8%, all P ≤ 0.0001), with similar effects observed at week 52. Correlations at baseline of pain/discomfort with signs and symptoms of AD were low to moderate.

Conclusions

Pain/discomfort, present in a substantial proportion of patients with moderate-to-severe AD, was significantly reduced by dupilumab treatment. Given the low-to-moderate correlations with other AD symptoms at baseline, pain likely represents a distinct AD symptom.

Trial registration

ClinicalTrials.gov identifiers NCT01859988, NCT02277743, NCT02277769, NCT02260986, and NCT02755649.

SUBMITTER: Silverberg JI

PROVIDER: S-EPMC8560147 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Publications

Dupilumab Significantly Modulates Pain and Discomfort in Patients With Atopic Dermatitis: A Post Hoc Analysis of 5 Randomized Clinical Trials.

Silverberg Jonathan I JI Simpson Eric L EL Guttman-Yassky Emma E Cork Michael J MJ de Bruin-Weller Marjolein M Yosipovitch Gil G Eckert Laurent L Chen Zhen Z Ardeleanu Marius M Shumel Brad B Hultsch Thomas T Rossi Ana B AB Hamilton Jennifer D JD Orengo Jamie M JM Ruddy Marcella M Graham Neil M H NMH Pirozzi Gianluca G Gadkari Abhijit A

Dermatitis : contact, atopic, occupational, drug 20211001 1S

<h4>Background</h4>Pain is a frequent symptom of atopic dermatitis (AD).<h4>Objectives</h4>The aims of the study were to evaluate the effects of dupilumab on pain/discomfort in AD and to determine whether pain correlates with other outcomes.<h4>Methods</h4>This was a post hoc analysis of 5 randomized, placebo-controlled clinical trials in which adults with chronic AD received placebo or dupilumab 300 mg every 2 weeks or once weekly with and without topical corticosteroids. Proportions of patient ...[more]

PMID: 33165005

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Project description:ImportanceErythrodermic atopic dermatitis (AD) is a severe AD subtype defined by extensive skin involvement, leading to complications and sometimes hospitalization.ObjectiveTo assess dupilumab's efficacy and safety in patients with erythrodermic AD in clinical trials.Design, setting, and participantsThis post hoc analysis included patients enrolled in 6 multicenter, multinational, randomized, double-blind, placebo-controlled trials. Patients included in this analysis met erythrodermic AD criteria of 90% or greater body surface area (BSA) affected by AD and Global Individual Sign Score for erythema of 1 or higher. Data analyses for this post hoc analysis were conducted between March 5, 2019, and October 24, 2020.InterventionsDupilumab once weekly or every 2 weeks, or placebo, either as monotherapy or with concomitant topical corticosteroids (TCS).Main outcomes and measuresEfficacy (BSA, Eczema Area and Severity Index [EASI] score, Peak Pruritus Numerical Rating Scale [PP-NRS] score), changes in serum biomarkers (thymus and activation-regulated chemokine, total immunoglobulin E, lactate dehydrogenase), and safety (incidence of adverse events) at week 16. Data were pooled within each regimen; monotherapy and concomitant TCS results are shown separately.ResultsOf 3075 randomized patients, 209 met criteria for erythrodermic AD at baseline, with the median age being 31 and 39 years in the monotherapy and concomitant TCS trials, respectively, similar to the overall populations (34 and 36 years, respectively); 71.3% (n = 97) and 74.0% (n = 54) of patients, respectively, were male (compared with 58.7% and 60.6% in the overall populations). In patients with erythrodermic AD, dupilumab once weekly and every 2 weeks vs placebo significantly improved percentage of BSA affected by AD (least squares mean percent change [SE]) with monotherapy (-42.0% [7.7%] and -39.9% [6.5%] vs -17.2% [11.0%]; P = .03) and concomitant TCS (-63.2% [6.7%] and -56.1% [9.1%] vs -14.5% [7.3%]; P < .001); EASI score with monotherapy (-58.5% [9.0%] and -58.3% [7.9%] vs -22.3% [12.4%]; P = .004 and P = .003, respectively) and concomitant TCS (-78.9% [7.8%] and -70.6% [10.1%] vs 19.3% [8.2%]; P < .001); and PP-NRS score in monotherapy (-45.9% [7.8%] and -33.9% [6.6%] vs -0.6% [9.4%]; P < .001) and concomitant therapy (-53.0% [8.1%] and -55.7% [10.8%] vs -26.0% [8.8%]; P = .006 and P = .01, respectively). Nominally statistically significant improvement was seen as early as week 1 (EASI and PP-NRS scores with monotherapy). Biomarker levels were significantly reduced vs placebo. The most frequent adverse events in dupilumab-treated patients were injection-site reaction, conjunctivitis, and nasopharyngitis.Conclusions and relevanceIn this post hoc analysis of 6 randomized clinical trials, treatment with dupilumab resulted in rapid, sustained improvements in AD signs and symptoms with acceptable safety in patients with erythrodermic AD, similar to those in the trials' overall patient population.Trial registrationClinicalTrials.gov Identifiers: NCT01859988, NCT02277743, NCT02277769, NCT03054428, NCT02260986, NCT02755649.

Project description:BackgroundPatients with moderate-to-severe atopic dermatitis (AD) have increased infection risk, including skin infections and systemic infections. Immunomodulators (e.g., anti-tumor necrosis factors, anti-interleukin [anti-IL]-23, anti-IL-17, Janus kinase inhibitors) increase risk of infections. Dupilumab (a monoclonal antibody blocking the shared receptor component for IL-4 and IL-13) is approved for inadequately controlled moderate-to-severe AD and for moderate-to-severe eosinophilic or oral corticosteroid-dependent asthma.ObjectiveThe aim was to determine the impact of dupilumab on infection rates in patients with moderate-to-severe AD.MethodsThis analysis pooled data from seven randomized, placebo-controlled dupilumab trials in adults with moderate-to-severe AD. Exposure-adjusted analyses assessed infection rates.ResultsOf 2932 patients, 1091 received placebo, 1095 dupilumab 300 mg weekly, and 746 dupilumab 300 mg every 2 weeks. Treatment groups had similar infection rates overall per 100 patient-years (placebo, 155; dupilumab weekly, 150; dupilumab every 2 weeks, 156; dupilumab combined, 152), and similar non-skin infection rates. Serious/severe infections were reduced with dupilumab (risk ratio 0.43; p < 0.05), as were bacterial and other non-herpetic skin infections (risk ratio 0.44; p < 0.001). Although herpesviral infection rates overall were slightly higher with dupilumab than placebo, clinically important herpesviral infections (eczema herpeticum, herpes zoster) were less common with dupilumab (risk ratio 0.31; p < 0.01). Systemic anti-infective medication use was lower with dupilumab.ConclusionsDupilumab is associated with reduced risk of serious/severe infections and non-herpetic skin infections and does not increase overall infection rates versus placebo in patients with moderate-to-severe AD. CLINICALTRIALS.Gov identifiersNCT01548404, NCT02210780, NCT01859988, NCT02277743, NCT02277769, NCT02260986, and NCT02755649.

Project description:BackgroundConjunctivitis is a known comorbidity of atopic dermatitis. Dupilumab clinical trials for moderate-to-severe atopic dermatitis in adults showed a higher conjunctivitis incidence for dupilumab-treated patients than placebo-treated patients, whereas trials for uncontrolled asthma reported lower rates for both dupilumab and placebo.ObjectiveThe objective of this study was to evaluate the incidence and severity of conjunctivitis in dupilumab clinical trials in adolescents with moderate-to-severe atopic dermatitis or uncontrolled asthma.MethodsWe evaluated the incidence of conjunctivitis in adolescents (aged 12 to < 18 years) in three phase III trials. Ocular events were diagnosed and treated based on patient-reported symptoms and an external eye examination by study investigators, in most cases without an ophthalmologic referral. In LIBERTY AD ADOL (16-week, randomized, placebo-controlled, double-blinded trial), adolescents with moderate-to-severe atopic dermatitis were randomized to subcutaneous placebo, dupilumab 300 mg every 4 weeks, or dupilumab every 2 weeks (200 mg, patients < 60 kg at baseline; 300 mg, ≥ 60 kg at baseline). In LIBERTY AD PED-OLE (open-label extension), pediatric patients from previous dupilumab atopic dermatitis trials received dupilumab 2 mg/kg or 4 mg/kg weekly (up to 300 mg) or 300 mg every 4 weeks. In LIBERTY ASTHMA QUEST (randomized, double-blinded, placebo-controlled trial), patients with uncontrolled moderate-to-severe asthma were randomized to 52 weeks of add-on therapy with dupilumab 200 or 300 mg every 2 weeks or matched-volume placebo.ResultsIn ADOL, more dupilumab-treated (17/165; 10.3%) than placebo-treated patients (4/85; 4.7%) reported one or more conjunctivitis event. All events were mild to moderate in severity; 12 (7.3%) dupilumab-treated and 4 (4.7%) placebo-treated patients received treatment. Most patients with conjunctivitis (dupilumab, 12/17; placebo, 4/4) recovered/resolved during the treatment period. The risk of conjunctivitis showed no relationship with dupilumab serum concentration. In PED-OLE, 12/275 adolescents (4.4%) reported one or more conjunctivitis event. Most conjunctivitis events were mild to moderate. Ten patients received treatment for conjunctivitis. Ten patients recovered/resolved during the study. In QUEST, similar low proportions of dupilumab-treated (2/68, 2.9%) and placebo-treated (1/39, 2.6%) adolescents reported one or more conjunctivitis event. All events were mild to moderate. One dupilumab-treated patient received treatment for conjunctivitis. All cases recovered/resolved during the study. No patients in these trials discontinued study treatment temporarily or permanently because of conjunctivitis. In ADOL, one case of unspecified viral keratitis (specific viral etiology not known) in the dupilumab 300-mg every 4 weeks group and one case of allergic blepharitis in the placebo group were reported; both events resolved during the treatment period, and neither led to treatment discontinuation.ConclusionsDupilumab-treated adolescents in atopic dermatitis trials had a higher incidence of conjunctivitis than placebo-treated patients, whereas overall rates of conjunctivitis among adolescents in the asthma trial were lower than in atopic dermatitis trials and were similar for dupilumab- and placebo-treated patients. Most events were mild to moderate, most recovered/resolved, and none prompted study withdrawal. These results are similar to those reported in adult trials and support a drug-disease interaction. CLINICALTRIALS.Gov identifiersNCT03054428, NCT02612454, NCT02414854. Conjunctivitis in Dupilumab Clinical Trials for Adolescents with Atopic Dermatitis or Asthma (MP4 18453 kb).

Project description:IntroductionPrimary results of the JADE DARE trial (NCT04345367) demonstrated that abrocitinib was superior to dupilumab in reducing the signs and symptoms of moderate-to-severe atopic dermatitis (AD). This post hoc analysis evaluated the efficacy and safety of abrocitinib in patients with moderate-to-severe AD who were responders or nonresponders to dupilumab using various definitions of response.MethodsData included dupilumab-treated patients from JADE DARE who switched to abrocitinib 200 mg when enrolled in the ongoing JADE EXTEND trial (NCT03422822). For this analysis, various response criteria at Week 26 of JADE DARE were defined post hoc based on Investigator's Global Assessment (IGA), Eczema Area and Severity Index (EASI), Peak Pruritus Numerical Rating Scale (PP-NRS), and Dermatology Life Quality Index (DLQI) scores or responses. Efficacy was analyzed at Week 12 of JADE EXTEND based on patients' fulfillment of the various response criteria at Week 26 of JADE DARE. EASI scores and percentage changes from baseline in EASI and PP-NRS at Week 26 in JADE DARE were compared with the corresponding scores and percentage changes at Week 12 in EXTEND. Safety was assessed.ResultsOf 365 dupilumab-treated patients in JADE DARE, 316 were enrolled in JADE EXTEND and 312 received abrocitinib 200 mg. Most dupilumab responders for IGA, EASI, PP-NRS, and DLQI at DARE Week 26 maintained their responses 12 weeks after switching to abrocitinib, while a considerable proportion of IGA, EASI, PP-NRS, or DLQI dupilumab nonresponders gained response after switching to abrocitinib. Lower EASI scores and greater percentage changes from baseline in EASI and PP-NRS scores were observed with abrocitinib at EXTEND Week 12 than with dupilumab at DARE Week 26. No new safety signals were observed.ConclusionAbrocitinib 200 mg may be an effective treatment option for patients with moderate-to-severe AD who do not achieve an optimal response with dupilumab treatment.Clinical trial registrationClinicaltrials.gov: NCT04345367 (JADE DARE) and NCT03422822 (JADE EXTEND).

Project description:IntroductionAdults with atopic dermatitis (AD) commonly report adult-onset disease. AD is associated with different genetics, lesion morphology and distribution, and symptoms by age of onset. Yet little is known about possible differences in treatment efficacy between adults with adult-onset or childhood-onset AD.MethodsWe evaluated the efficacy of dupilumab by age of AD onset in adults with moderate-to-severe AD, using pooled data from the LIBERTY AD SOLO 1 and 2 studies (NCT02277743, NCT02277769). Results were stratified based on self-reported age of AD onset, divided into four age subgroups: 0-4, 5-9, 10-19, and over 20 years.ResultsThis analysis included 460 patients treated with placebo and 457 treated with dupilumab 300 mg every 2 weeks (q2w), with a mean patient age of 38 years. Most patients (53.2%) reported AD onset at 0-4 years, with 14% at 5-9 years, 13.4% at 10-19 years, and 18.5% at 20 years or older. Dupilumab significantly improved AD signs and symptoms over 16 weeks compared with placebo, regardless of age of onset. Dupilumab treatment resulted in a significantly greater proportion of patients achieving Eczema Area and Severity Index (EASI)-50, EASI-75, and EASI-90 (50%, 75%, and 90% improvement from baseline EASI, respectively), and clear or almost clear skin (Investigator's Global Assessment score 0 or 1) across all age-of-onset subgroups compared with placebo. In addition, EASI improvements were significant across all anatomical regions in all subgroups. Weekly average peak pruritus Numerical Rating Scale and Dermatology Life Quality Index also improved consistently and significantly with dupilumab versus placebo, regardless of age of onset.ConclusionDespite possible differences in presentation and progression of AD linked to age of onset, dupilumab showed similar significant and sustained improvements in AD signs, symptoms, and quality of life in adults compared with placebo, over 16 weeks of treatment.Trial registrationLIBERTY AD SOLO 1: NCT02277743; LIBERTY AD SOLO 2: NCT02277769. Infographic available for this article.

Project description:BACKGROUND:Atopic dermatitis is a chronic inflammatory condition with substantial burden and limited treatment options for adolescents with moderate-to-severe disease. Significantly more patients treated with dupilumab vs. placebo achieved Investigator's Global Assessment 0/1 at week 16. OBJECTIVE:The objective of this study was to assess the impact of dupilumab treatment vs. placebo on the achievement of clinically meaningful improvements in atopic dermatitis signs, symptoms and quality of life. METHODS:R668-AD-1526 LIBERTY AD ADOL was a randomized, double-blinded, parallel-group, phase III clinical trial. Two hundred and fifty-one adolescents with moderate-to-severe atopic dermatitis received dupilumab 300 mg every 4 weeks (q4w; n = 84), dupilumab 200 or 300 mg every 2 weeks (q2w; n = 82), or placebo (n = 85). A post-hoc subgroup analysis was performed on 214 patients with Investigator's Global Assessment > 1 at week 16. Measures of atopic dermatitis signs, symptoms, and quality of life were assessed. Clinically meaningful improvement in one or more of three domains of signs, symptoms, and quality of life was defined as an improvement of ≥ 50% in Eczema Area and Severity Index, ≥ 3 points in Peak Pruritus Numerical Rating Scale, or ≥ 6 points in the Children's Dermatology Life Quality Index from baseline. RESULTS:Of patients receiving dupilumab q2w, 80.5% [66/82] experienced clinically meaningful improvements in atopic dermatitis signs, symptoms, or quality of life at week 16 (vs. placebo, 20/85 [23.5%], difference 57.0% [95% confidence interval 44.5-69.4]; q4w vs. placebo, 53/84 [63.1%], difference 39.6% [95% confidence interval 25.9-53.3]; both p < 0.0001). Results were similar in adolescents with Investigator's Global Assessment > 1 at week 16 (q2w, 46/62 [74.2%] vs. placebo, 18/83 [21.7%], difference 52.5% [95% confidence interval 38.5-66.6]; q4w, 38/69 [55.1%] vs. placebo, difference 33.4% [95% confidence interval 18.7-48.1]; both p < 0.0001). CONCLUSIONS:Dupilumab provided clinically meaningful improvements in signs, symptoms, and quality of life in adolescents with moderate-to-severe atopic dermatitis among patients with Investigator's Global Assessment > 1 at week 16. Treatment responses should be interpreted in the context of such clinically relevant patient-reported outcome measures. TRIAL REGISTRATION:ClinicalTrials.gov; NCT03054428. Adolescents with atopic dermatitis: does dupilumab improve their signs, symptoms, and quality of life? (MP4 212916 kb).

Dataset Information

Dupilumab Significantly Modulates Pain and Discomfort in Patients With Atopic Dermatitis: A Post Hoc Analysis of 5 Randomized Clinical Trials.

Background

Objectives

Methods

Results

Conclusions

Trial registration

Publications

Dupilumab Significantly Modulates Pain and Discomfort in Patients With Atopic Dermatitis: A Post Hoc Analysis of 5 Randomized Clinical Trials.

Similar Datasets

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